The Human Genome Project has made it possible to study biology and disease at the genetic and molecular level using high-throughput technologies. The NIH Chemical Genomics Center (NCGC) collaborates with researchers throughout the world to discover small molecule chemical probes of novel genes, pathways, and cellular phenotypes relevant to health and disease. The NCGC, together with the extramural centers of the Molecular Libraries Screening Center Network, is exploring the enormous number of proteins (numbering well over 100,000) encoded by the human and other genomes for which no small molecule chemical probes have been identified. In so doing, this initiative promises to significantly improve the understanding of mechanisms by which genes and their protein products function and accelerate the development of therapies for human diseases based on knowledge of the genome. This year has seen a dramatic increase in the NCGC's capacities, increasing staff from 19 to 30, and moving operations from start-up into production. The NCGC currently has over 20 active collaborations with researchers in the intramural, extramural, and pharma/biotech sectors. In this reporting period, the NCGC performed 28 screens comprising over 10 million miniaturized assays, and desposited over 7 million data fields to the public PubChem database. During this year, the NCGC developed a new screening paradigm, called Quantitative High Throughput Screening (qHTS), that generates dramatically better screening data than conventional HTS; this was published in the Proceedings of the National Academy of Sciences in August 2006.